From 2009-2014, I was PI on a NIH Phase I & II SBIR with 4D Technology Corporation to develop a bio-phase imaging system based upon a Linnik interference microscope using dynamic quantitative phase-measuring microscopy (QPM) in real-time.

The animated image above shows real-time beating of live cardiac myocytes grown on a slide and imaged using the QPM described above. It was wonderful to discover that we could image these kinds of cellular contractions without the use of any toxic dyes or fluorescent markers and watch cellular processes with minimal perturbation.

The middle movie shows the optical phase topography of a pond critter waving its cilia in water. It is trapped under a coversliip so it doesn't swim away.

The bottom movie shows the optical phase thickness of a swimming protozoa in real time.

My goal in these endeavors has been to work toward non-invasive imaging techniques to image and monitor cellular processes.

The selected articles below provide a good overview of the project. Scroll down the page to see more results, videos and listings of relevant articles.

Imaging of blood flow through the cardinal vein in a 3-day old live anesthetized Zebrafish at 15 fps. Colors indicate relative optical thickness. 511nm source, 40X magnification, and 33 x 44 micron field of view. Thicker/denser areas are red, and thinner/less dense areas are blue. [Co-Author: Goldie Goldstein; Zebrafish preparation by Maki Niihori, University of Arizona].

Growth of oligodendrocytes at 1 frame per minute observing branching at the ends of processes. Colors indicate relative optical thickness. Thicker/denser areas are red, and thinner/less dense areas are blue. [Co-Author: Goldie Goldstein; Research partners: Jane Peppard et al., Sanofi-Aventis].

[top] Myocyte growth with 10fps burst intervals over 1hr 20min at 40X with 511nm source and 211 x 211 micron area. Scaled to enhance membrane ruffling. Colors indicate relative optical thickness. [bottom] Vesicle transport in myoblasts with 511nm source, 40X, over 14 min. Thicker/denser areas are red, and thinner/less dense areas are blue. [Co-Author: Goldie Goldstein; Research partners: Jane Peppard et al., Sanofi-Aventis].

(A) Epithelial cell, (B) simulated DIC, (C) simulated dark field (gradient magnitudes), and (D) cell edges imaged on reflective slide at 40X. [Co-Author: Goldie Goldstein]

(A) Epithelial cells, (B) simulated DIC, (C) simulated dark field (gradient magnitudes), and (D) cell edges imaged on bare glass slide at 20X. [Co-Author: Goldie Goldstein]

A nassula with engorged food vacuoles (bumps) as it moves through pond water.

Several imaging modes (shown top to bottom) highlight different aspects of the cell structure. A movie, created from a series of these images, quantifies the changes in the protozoan’s size, shape and structure over time. Three frames of that movie are shown for each imaging mode.

The nassula is 50x80 microns in size—roughly the width of a human hair.

This movie gives an overview of the system developed through an NIH SBIR Phase II Grant. [Movie produced by Howard Letovsky, Letovsky Dynamics].